"He does not appear to understand how desperate the problem in Zimbabwe is, and the solutions he proposes are too small," Tsvangirai said in a statement issued as Mbeki chaired a new round of mediation talks.
"He is not serving to bring the parties together because he does not understand what needs to be done."
Mbeki brokered a power-sharing deal signed by Tsvangirai and President Robert Mugabe two months ago, but the plan to form a unity government has run aground over disputes on the balance of power between the two parties.
Tsvangirai said he had written to South African President Kgalema Motlanthe "detailing the irretrievable state of our relationship with Mr Mbeki and asking that he recuse himself".
The statement appeared to signal the end of two days of talks presided over by Mbeki in South Africa aimed at saving the deal.
The MDC leader said he remained committed to the unity accord, but accused Mbeki of siding with Mugabe’s Zanu-PF party in the negotiations.
"His partisan support of Zanu-PF, to the detriment of genuine dialogue, has made it impossible for the MDC to continue negotiating under his facilitation," Tsvangirai said.
"The Mugabe team negotiates as though their priority is to cover up the problem rather than solve it.